Keloids are dermal tumors that occur in response to trauma. A hereditary predisposition to keloidformation occurs with high frequency in black populations. In vivo, prolonged proliferation of fibroblasts and over-production of collagen and proteoglycans are observed. We are attempting to identify the primary gene defect causing this tumor and its mode of action by studying growth and matrix metabolism of cultured fibroblasts derived from keloids and from normal skin and scar tissue. We have shown that cells from keloids differ from normal fibroblasts in their response to hydrocortisone (HC). Growth and ornithine decarboxylase activity of normal cells are stimulated while they are not in keloid cells; collagen and proteoglycan synthesis are much less inhibited in keloid than in normal cells; and System A amino acid transport is stimulated 2-fold in normal but 10-fold in keloid cells. Regulation of all of these processes is mediated by the glucocorticoid receptor, but the altered response to HC by keloid cells is not due to differences in number of glucocorticoid receptors, steroid-binding affinity, or nuclear binding of the steroid-receptor complex. In both normal and keloid cells, glucocorticoid induction of amino acid transport appears to require RNA and protein synthesis, involves a proportional increase in Vmax of System A, and is not attributable to differences in membrane potential, which suggests induced synthesis of a System A component. While showing that glucocorticoid induction of System A activity was directly proportional to concentration of steroid-receptor complex in both normal and keloid cells, we discovered that physiological concentrations of insulin were required for the induction. Inhibitor studies suggest that insulin is involved after synthesis and posttranslational modification of the transporter. No differences were observed between normal and keloid cells with regard to the insulin requirement for glucocorticoid induction of System A. (S)